The objectives of the work proposed are: 1. To establish the capability to do three-dimensional structure analysis on complex biological structures by electron microscopy; 2. To apply this capability to crystalline cell membrane materials and other suitable specimens, at the highest resolution consistent with the properties of the specimen material and the performance of the electron microscope; 3. To innovate new methods of specimen preparation that will make it possible to perform electron-microscopy structure analysis at higher resolution, and additional methods that will extend the existing capabilities to free-standing (i.e., non-crystalline) particles; 4. To investigate alternative methods for improving the present-day instrumental resolving power (Scherzer limit) of approximately 3.5A down to the level of atomic resolution, that is, to the level of 1.5A to 2.0A.